One of the most exciting recent developments in the field of cytoskeleton is the discovery that FtsZ, a bacterial cell division protein, is a homologue of tubulin. The homology was first indicated by its GTPase activity, then by very compelling sequence identities between FtsZ and all tubulins. Two laboratories recently demonstrated that FtsZ could form polymers, but their structural relation to microtubules was not clear. Our lab has now demonstrated that FtsA will polymerize into protofilaments, sheets an rings that are strikingly similar to polymers formed by eukaryotic tubulins. FtsZ appears to be the major bacterial cytoskeletal protein, forming a (contractile?) ring at the site of septation. We calculate that the 10,000 molecules of FtsZ per cell are sufficient to make a single protofilament that encircles the bacterium 23 times, more than sufficient to form a contractile ring of anti-parallel filaments. The physiological polymer of FtsZ is still not known, but may be a small sheet or bundle of protofilaments. The first goal of our studies is to determine the range of polymer forms in different solution conditions, using negative stain and rotary shadowing electron microscopy. From this we hope to deduce the structures that are likely to operate at the septation furrow. We are especially interested in how GTP is utilized in the polymerization of FtsZ, to compare with the GTPase in microtubule assembly and dynamic instability. We propose to clone FtsZ from several other bacterial species, in particular Azotobacter, which may have a [prokaryotic microtubule - the missing link in evolution of microtubules. We also propose to search for a mouse mitochondrial FtsZ, based on the very recent discovery of chloroplast FtsZ in Arabidopsis. We plan to study the polymers of the chloroplast FtsZ in collaboration with Dr. Osteryoung, who has cloned it, and eventually hope to characterize the polymers of mouse mitochondrial FtsZ. Chloroplast and mitochondrial FtsZ may be involved in division of these organelles. FtsZ offers excellent prospects for x-ray crystallography, and may provide solutions to the several problems that have prevented any crystallography of eukaryotic tubulins. Because they are homologous proteins, an atomic structure of FtsZ will also provide most of the structure of tubulin. Several bacterial proteins are already known that interact with FtsZ, and others must exist. We are particularly interested in SulA, which blocks FtsA function and may b e monomer-binding or a capping protein. Anchor proteins that traverse the inner membrane and may nucleate polymer assembly will be sought. Finally, we believe that motor proteins interacting with FtsZ are likely to exist, an propose to search for prokaryotic homologues of kinesin or dynein.